Our studies continue to focus on the identification of signal transduction pathways that are critical for Epo regulated signaling in erythrocytes. The studies have demonstrated that the Epo receptor initiates a number of pathways that are either redundant or not required for function. This is based on extensive studies to date on two receptor mutant, knockin strains of mice (H and HM). The H mutant mice have a receptor that lacks the distal half of the cytoplasmic domain and retains only one tyrosine. The HM mutant mice have the truncated receptor that also contains a mutation that eliminates the last tyrosine. Relatively minor consequences are associated with these mutations and demonstrate that the distal region and tyrosine are not required fo receptor function. Using these mutants we have focused on genes that are specifically regulated by the mutant receptors. Studies have been completed on several genes that are targets of Stat5 including GADD45 gamma and two genes SG-1 and SG-3. To evaluate the functions of these genes mouse mutant strains were created in which the genes were deleted. In none of the cases did the deletions have a consequence on the phenotypic properties of the mice indicating that they either function redundantly to other pathways or have no function within the context of normal hematopoesis, or in general development. Studies seek to continue to identify genes that are critical to erythropoiesis and that are regulated by Epo signaling.